Cardiomyocytes of Chronically Ischemic Pig Hearts Express the MDR-1 Gene-encoded P-glycoprotein

Abstract

S U M M A R YThe multidrug-resistant (MDR)-1 gene-encoded P-glycoprotein (Pgp-170) is not normally present in the cardiomyocyte. Given that in other tissues Pgp-170 is not found under normoxic conditions but is expressed during hypoxia, we searched for Pgp-170 in chronically ischemic porcine cardiomyocytes. Pgp-170 was detected and localized via immunohistochemistry in ischemic and nonischemic cardiomyocytes of eight adult pigs 8 weeks after placement of an Ameroid constrictor at the origin of the left circumflex artery (Cx). Regional myocardial ischemia in the Cx bed was documented with nuclear perfusion scans. Pgp-170 mass was quantified using Western blot analysis. In all pigs, Pgp-170 was consistently present in the sarcolemma and T invaginations of the cardiomyocytes of the ischemic zone. Pgp-170 expression decreased toward the border of the ischemic zone and was negative in nonischemic regions as well as in the myocardium of sham-operated animals. Western blot analysis yielded significantly higher Pgp-170 mass in ischemic than in nonischemic areas. We conclude that Pgp-170 is consistently expressed in the cardiomyocytes of chronically ischemic porcine myocardium. Its role in the ischemic heart as well as in conditions such as myocardial hibernation, stunning, and preconditioning may have potentially relevant clinical implications and merits further investigation.

Role of Multidrug Resistance Protein 3 in Antifungal-Induced Cholestasis

“…Membranes isolated from Caco-2 cells were used as the positive control for MDR1 (Hosoya et al, 1996; Uchida Figure 5A shows the corresponding immunoblot using an MDR3-specific antibody known to not cross react with MDR1 (Scheffer et al, 2000), and hence not generating a signal in WT and Caco-2 cells. We also used an MDR1-specific antibody (Georges et al, 1990) known to cross react with pMDR1 (Lazarowski et al, 2005) and found only a faint signal above the background in WT and BNMG cells (data not shown). Combined, these data demonstrate that expression of pMDR1 in our cell lines is minimal and that the C 6 -NBD-PC secretion into the apical compartment is mediated by MDR3.…”

Plasmid-mediated VEGF gene transfer induces cardiomyogenesis and reduces myocardial infarct size in sheep

“…6 Sca-1 and c-kit immunostainings of cardiomyoblasts were negative because the commercial kits we used did not react with ovine antigens. The same antibodies did react with murineand human-positive controls.…”

ABCB1 genotype and PGP expression, function and therapeutic drug response: a critical review and recommendations for future research

“…Disease states themselves may also influence PGP expression or may themselves be associated with polymorphisms in ABCB1. For example, chronically ischaemic cardiomyocytes in pigs have been shown to express PGP, whereas normal cells do not, 33 PGP expression and activity has been shown to be different in mouse models of colitis, 34 and inflammatory bowel disease has been reported to be associated with the 2677G4TA polymorphism. 35 Therefore, any study attempting to correlate genotype to expression levels should make efforts to control for the potential effects of co-morbidities, co-medications and their dosages.…”